Here, we show that intravenous (i.v.)or intranasal (i.n.)administration of apolipoprotein E peptide (ApoE)‐directed polymersome CpG nanoformulation (t‐NanoCpG) mediates efficient brain delivery of CpG, inducing strong immunotherapy of highly malignant murine LCPN glioma (Figure 1a). The gene discussed is APOE; the disease is central nervous system cancer.